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Structure-Function Analyses of a Keratin Heterotypic Complex Identify Specific Keratin Regions Involved in Intermediate Filament Assembly

Title
Structure-Function Analyses of a Keratin Heterotypic Complex Identify Specific Keratin Regions Involved in Intermediate Filament Assembly
Authors
Lee, Chang-HunKim, Min-SungLi, ShuangLeahy, Daniel J.Coulombe, Pierre A.
DGIST Authors
Lee, Chang-Hun
Issue Date
2020-03
Citation
Structure, 28(3), 355-362.e4
Type
Article
Article Type
Article
Author Keywords
intermediate filamentkeratinocyteskinepitheliumself-assemblycrystal structureepidermolysis bullosa simplexstructural proteincytoskeleton2B domain
Keywords
EPIDERMOLYSIS-BULLOSA SIMPLEX2B ROD DOMAINCOILED-COILMOLECULAR ARCHITECTURECRYSTAL-STRUCTUREATOMIC-STRUCTUREPOINT MUTATIONSCROSS-LINKINGVIMENTINDISEASE
ISSN
0969-2126
Abstract
Intermediate filaments (IFs) provide vital mechanical support in a broad array of cell types. Interference with this role causes cell fragility and accounts for a large number of human diseases. Gaining an understanding of the structure of IFs is paramount to understanding their function and designing therapeutic agents for relevant diseases. Here, we report the 2.6-Å resolution crystal structure of a complex of interacting 2B domains of keratin 5 (K5) and K14. K5 and K14 form a long-range, left-handed coiled coil, with participating α helices aligned in parallel and in register. Follow-up mutagenesis revealed that specific contacts between interacting 2B domains play a crucial role during 10-nm IF assembly, likely at the step of octamer-octamer association. The resulting structural model represents an atomic-resolution visualization of 2B-2B interactions important to filament assembly and provides insight into the defects introduced by mutations in IF genes associated with human skin diseases. © 2020 Elsevier Ltd Our understanding of the assembly and structure of 10-nm keratin intermediate filaments remains superficial. Here, Lee et al. report on the crystal structure of 2B domain heterocomplexes from keratin 5 and keratin 14. Mutagenesis studies highlight 2B-2B molecular interactions that are poised to sustain filament elongation during polymerization. © 2020 Elsevier Ltd
URI
http://hdl.handle.net/20.500.11750/11592
DOI
10.1016/j.str.2020.01.002
Publisher
Cell Press
Related Researcher
  • Author Lee, Chang-Hun Biointerface Structure and Skin Lab
  • Research Interests Structure-Function relationship of cytoskeletal proteins and membrane proteins; Structure-based design of biomolecules and drugs; Development of drug delivery system in skin
Files:
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Collection:
Department of New BiologyETC1. Journal Articles


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